This work aimed to study the risk assessment procedures of a combination of single and repeated dose of the widely used pesticide, ethoprophos (Etho) and heavy metal cadmium (Cd), on the hematological, biochemical, reproduction and cytogenetic parameters in male mice. The results revealed that the sub-lethal dose (1/50 LD₅₀) of the tested toxic substances (Etho and/or Cd) reduced the body and organ weights, the most hematological profile and the activity of acetylcholine esterase (AChE). The tested pollutants significantly increased the parameters of liver function, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as well as renal function tests, including creatinine and urea. In addition, they have deleterious effects on reproductive function tests by stimulating the number of sperm abnormalities (SA) and cytogenetic assays by increasing the frequency of chromosomal abnormalities (CA) and the mitotic index (MI). The overall results of this exploratory study suggest that the co-existence of the two tested compounds (Etho and Cd) had the propensity to cause a more pronounced effect than that of each compound alone on all the battery measured biomarkers, especially in the repeated treatment (14 doses) than that in the single one. Also, the combination of a range of simple and sensitive assays as endpoints gives a comprehensive picture and provides better insights to evaluate the potential effects of other commonly encountered environmental pollutants.